Animal feed for obtaining increased production in animals

ABSTRACT

AN ANIMAL FEED COMPRISING A COMPOUND OF THE GROUP CONSISTING OF AN OXAZINOBENZODIAZEPINE OF THE FORMULA:   1-R5,2(R6=),3-R7,5-(O=),6-R8,7-(R8-CH2-),8A-(R3,R4-   PHENYL),R1,R2-1,2,3,5-TETRAHYDRO-1,3-OXAZINO(3,2-D)(1,4)-   BENZODIAZEPINE   WHEREIN R1, R2, R3 AND R4 ARE SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL AND ALKOXY OF 1 TO 6 CARBON ATOMS, INCLUSIVE, HALOGEN, -CF3, -NO2 AND -CN; WHEREIN R5 IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL DEFINED AS ABOVE, AND BENZYL; WHEREIN R6 IS SELECTED FROM THE GROUP CONSISTING OF =O AND =S; WHEREIN R7 IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL DEFINED AS ABOVE, AND ALKOXY DEFINED AS ABOVE; AND WHEREIN R8 IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN, ALKYL DEFINED AS ABOVE, AND PHENYL IN COMBINATION WITH THE NUTRIENT FEED.

United "States Patent Officc 3,780,179 Patented Dec. 18, 1973 ANIMAL FEED FOR OBTAINING INCREASED PRODUCTION IN ANIMALS Robert J. Collins, Portage, Mich., assignor to The Up ohn Company, Kalamazoo, Mich.

No Drawing. Filed Aug. 9, 1971, Ser. No. 170,327 Int. Cl. A61k 27/00 US. Cl. 424-248 6 Claims ABSTRACT OF THE DISCLOSURE An animal feed comprising a compound of the group consisting of an oxazinobenzodiazepine of the formula:

wherein R R R and R are selected from the group consisting of hydrogen, alkyl and alkoxy of 1 to 6 carbon atoms, inclusive, halogen, --CF N and -CN; wherein R is selected from the group consisting of hydrogen, alkyl defined as above, and benzyl; wherein R is selected from the group consisting of =0 and-=8; wherein R is selected from the group consisting of hydrogen, alkyl defined as above, and alkoxy defined as above; and wherein R is selected from the group consisting of hydrogen, alkyl defined as above, and phenyl in combination with the nutrient feed.

CROSS-REFERENCE TO RELATED APPLICATIONS This application is related to US. Pat. No. 3,573,282, issued Mar. 30, 1971.

BRIEF SUMMARY OF THE INVENTION Broadly the present invention encompasses a nutritionally adequate animal feed having dispersed therein a compound of the Formula 1 in suflicient concentration to provide increasing productivity and feed efiiciencies in healthy meat-producing, milk-producing or egg-laying animals. The invention also includes the process of feeding the composition to meat-producing, milk-producing or egg-laying animals.

DETAILED DESCRIPTION It has been found in recent years that meat-producing animals will gain more Weight and gain it faster when various classes of compounds such as vitamins, minerals, estrogens, antibiotics, and tranquilizers are added to the diet. Although the presently available compounds are useful, new materials are still being sought that would produce weight gains more rapidly, to a greater extent, more efliciently with respect to feed intake at a lower cost and without undesirable side effects.

It is now possible by use of the present invention to obtain unexpected results in the feeding of meat-producing, milk-producing, or egg-laying animals; that is to say, an increased rate of weight gain, an increased amount of weight gain, an increase in milk production, or increased rate of egg laying, as well as increased feed efficiency, can be obtained by the addition of minute quantities of a compound of the Formula 1 to the animals usual nutrient feed.

Compounds of the Formula 1 can be prepared by methods disclosed in US. Pat. No. 3,537,282, issued Mar. 30, 1971 and South African Pat. No. 69/5961 issued on Sept. 3, 1970.

Unless otherwise specified, all percentages are given on a weight-to-weight basis. The pound (1b.) weights given are avoirdupois units.

Feeding of the compositions of the present invention can commence for birds shortly after hatching and in the case of mammals, during the creep-feeding period of suckling animals when they are starting on solid food and, of course, after weaning. Feeding of the compositions is continued throughout the growing period, lactation period, or egg-laying period.

The total concentration of the compound of the Formula 1 in the feed composition is determined with regard to the species of animal, age, weight, and average amount of feed consumed daily. Preferably the compound of the Formula 1 is employed in the finished feed that will supply the animal with a daily intake of from 0.03 mg. to about 500 mg. per head per day.

The following table illustrates the range of compound of Formula 1 in milligrams daily dose per head per day for representative animals.

The foregoing dosage can generally be accomplished by providing irom about 250 mg. to about 25,000 mg. of a compound of the Formula 1 per ton of finished feed.

Advantageously a compound of the Formula 1 is supplied in the form of a liquid or solid premix wherein the concentration is -2000 times greater than the desired final concentration of the feed. For example, the compound of Formula 1 can be dissolved or suspended in a fluid vehicle such as corn oil, cottonseed oil, molasses, distillers solubles and the like to prepare a fluid premix. Alternatively, a solid premix can be prepared by mixing a compound of the Formula 1 with an edible solid diluent such as sucrose, lactose, starch, corn meal, flour, calcium carbonate, soybean meal and the like.

EXAMPLE 1 A diet for fattening lambs is prepared from the following types and amounts of ingredients:

1 Contains the following percent of minerals: Mn, 12; Co 0.08; Fe, 5.0; Cu, 0.4;-1,0.25; Zn, 07.

The above feed to be mixed, pelleted and offered to fattening lambs free-choice in conjunction with hay.

To 999 parts of the preceding feed is added 1 part of a premix composition prepared by mixing 1.4 gm. of 11- chloro 8,12b dihydro-2,8-dimethyl 12b phenyl-4H- [1,3]oxazino[3,2-d] [l,4]benzodiazepine-4,7(6H) dione with suflicient corn meal to make one pound.

The feeding composition so prepared supplies 1.4 mg. of 1l-chloro-S,12b-dihydro-2,8dimethyl-12b-phenyl-4H- [l,3]oxazino[3,2-d][1,4]benzodiazepine 4,7(6H) dione per pound or 3.1 parts per million.

The foregoing compositions is usefully fed to lambs for increased rate of weight gain and improved utilization of feed.

EXAMPLE 2 A chicken feed for broilers is prepared from the following types and amounts of ingredients:

Percent Yellow corn meal 67.35 Soybean oil meal 24.00 Menhaden fish meal 6.00 Steamed bone meal 1.00 Ground limestone 1.00 Iodized salt .34 25% choline chloride .13 Vitamin B supplement (6 mg./lb.) .10 Manganese sulfate .02 Supplemental vitamin mix .06

1 Consisting of 16.0 gm. Vitamin A supplement (10 units/ ing.); 3.6 gm. Vitamin D: supplement (15,000 units/gm}; 7.1 gm. riboflavin supplement (1 gm. riboflavin per ounce 500 mg. niacin,

ducks and geese.

EXAMPLE 3 A fattening feed for 800 pound yearling cattle is prepared from the following types and amounts of ingredients:

Percent Ground car com 89.75 Soybean oil meal, 44% 9.0 Ground limestone 0.7 Salt 0.5 Trace mineral mixture 0.05

' 1 Contains the following percent of minerals: Mn, 12; Co, 0.08; Fe, 5.0; Cu, 0.4; I, 0.24; Zn, 0.7.

To 999 parts of the preceding feed is added 1 part of a premix composition prepared by mixing 3.0 gm. of 11-chloro-8,12b-dihydro 2, 8 dimethyl 12b phenyl- 4H [1,3]oxazino[3,2-d] [1,4]benzodiazepine 4,7(6H)- dione with sufficient wheat flour to make 1 pound.

V The feeding compositions so prepared supplies 3.0 mg. of 11 chloro-8,12b-dihydro 2,8 dimethyl-lZb-phenyl- 41-1 [1,3]oxazino[3,2-d] [1,4]benzodiazepine 4,7(6H)- dione per pound, or about 6.6 parts per million.

Cattle are to receivethe foregoing feed ad libitum to gether with 5' lb. of hay perwihead per day and when so fed have an increased rate .of w ight gain and improved utilization of feed. e I

4 EXAMPLE 4 A swine diet for growing hogs of 40 to 100 pounds body weight is prepared from the following types and amounts of ingredients:

Percent Corn, ground 78.15 Soybean oil meal, 44% 17.0 Meat and bone scraps, 50% 3.0 Oyster shell flour 0.4 Bone meal 0.5 Salt 0.5 Trace mineral mixture 1 0.05 Zinc oxide 0.01 Vitamin A and D supplement 2 0.25 B vitamin supplement 0.05 Vitamin B supplement 0.09

1 Contains the following percent of minerals: Mn, 12; C0,, 0.08 Fe, 5.0; Cu, 0.4; I, .24 Zn, 0.7.

Contains 300 USP units Da/gm. and 1500 I.U.A./gm.

Contains per 11).: Riboflavin, 2000 mg.; calcium panifitlgrsate, 4000 mg.; niacin, 9000 mg.; and choline chloride,

l Contains 6 mg, Vitamin B12 per 1b.

Following the procedure of the preceding Examples 1 to 4, inclusive, animal feeds are similarly prepared substituting equimolar amounts of:

1 l-chloro-8,12b-dihydro-2-benzyl-3,12b-diphenyl-8- methyl-4H- 1,3 oxazino[ 3,2-d] [1,4] benzodiazepine-4,7 6H) -dione;

11-chl0r0-8,12b-dihydr0-2-methyl-l2b-phenyl-4H- [1,3 oxazino[3,2-d] [1,4] benzodiazepine-4,7 (6H) dione;

l l-chloro-8,12b-dihydro-2,8-dimethyl-IZb-(p-chlorophenyl)-4H-[1,3]oxazino[3,2fd] [1,4] benzodiazepine-4,7 6H -dione;

1 l-trifluoromethyl-S,12b-dihydro-2,8-dimethyl-12b-.

phenyl-4H- 1,3 oxazino [3,2-d] [1,4]benzodiazepine-4,7 6H)-dione;

11-chl0ro-8,12b-dihydro-2,8-dimethyl-12b-phenyl- 4H-[1,3]oxazino[3,2-d] [1,4] benzodiazepin-4- (6H) -one-7-thione;

1 1-cya-no-8,12b-dihydro-2,8-dimethy1-12b-phenyl- 4H-[1,3]oxazino[3,2-d] [1,4] benzodiazepine- 4,7 (6H) -dione;

1 1-nitro-8, l2b-dihydro-2,8-dimethyl- 12b-phenyl- 4H-[1,3]oxazino[3,2-d] [1,4] benzodiazepine- 4,7-( 6H -dione;

1 1-chloro-8, 12b-dihydro-3-ethyl-8-methyl-2-propyl- 12b-phenyl-4H-[1,3]oxazino[3,2-d] [1,4] benzodiazepine-4,7 (6H) -dione;

1 1-chloro-8,l2b-dihydro-2-ethyl-3,S-dimethyl-12bphenyl-4H-[ 1,3] oxazino[3,2-d] [1,4] benzodiazepine-4,7 (6H) -dione;

8,12b-dihydro-2,8-dimethyl-12b-phenyl-4H-[ 1,3]

oxazino [3,2-d] 1,4] benzodiazepine-4,7 6H) -dione;

1 1-methoxy-8,12b-dihydro-2, S-dimethyl- 12b-phenyl- 4H-[ 1,3 oxazino [3,2-d] 1,4] benzodiazepine- 4,7 (6H) -dione;

1 l-bromo-S, 12b-dihydro-2,8-dimethyl-1 2b-phenyl-4H- 

